The genes for several endothelial-leukocyte adhesion molecules implicated in the initiation of the atherosclerotic lesion contain functional NF-kappa B binding sites which are required for cytokine induction in endothelial cells. Activation of this pleiotropic family of transcription factors may explain in part the diversity of growth factor and cytokine gene expression associated with dysfunctional endothelium, as well as the increased endothelial cell replication observed at lesion prone anatomic sites. Endothelial oxidant stress and activation of the NF-kappa B family of transcription factors may link the otherwise seemingly diverse risk factors associated with the initiation of the atherosclerotic lesion into a final common pathway for induced endothelial gene activation.